Clopidogrel has the following structure (1)

It is available in the market as its bisulfate salt and is marketed by Sanofi-Synthelabo as “Plavix” having the general formula (II)

Clopidogrel is an inhibitor of platelet aggregation and is marketed as an antianginal agent, antiplatelet agent and is found to decrease morbid events in people with established atherosclerotic cardiovascular disease and cerebrovascular diseases.
The therapeutic application of Clopidogrel as blood-platelet aggregation inhibiting agents and antithrombotic agent and its preparation is disclosed in U.S. Pat. No. 4,529,596. U.S. Pat. No. 4,847,265 describes the process for the preparation of the hydrogen sulfate salt of Clopidogrel.
Polymorphs of Clopidogrel bisulfate has been described in U.S. Pat. Nos. 6,504,040 and 6,429,210. We have disclosed novel polymorphs of Clopidogrel bisulfate in our published application WO2004081016.
U.S. Pat. No. 4,847,265 discloses that the dextrorotatory enantiomer of formula (I) of Clopidogrel has an excellent antiaggregant platelet activity, whereas the corresponding levorotatory enantiomer of (I) is less tolerated of the two enantiomers and is less active. U.S. Pat. No. 4,847,265 also describes various other salts of Clopidogrel base as well as of the dextrorotatory isomer like its hydrochloride, carboxylic acid and sulfonic acids salts were prepared. Specifically salts of acetic, benzoic, fumaric, maleic, citric, tartaric, gentisic, methanesulfonic, ethanesulfonic, benzenesulfonic and lauryl sulfonic acids were prepared. However, according to the patent, these salts usually precipitated in amorphous form and/or they were hygroscopic making them difficult to handle in an industrial scale. Also, no process and no data corresponding to any of these salts are reported. The specification also describes salts of dobesilic acid (m.p.=70° C.) and para-toluenesulfonic acid, having a melting point of 51° C., the purification of which, as accepted in the patent, proved to be difficult.
Clopidogrel besylate which is at least partly in crystalline (solvated) forms have been disclosed by Helm in their published applications WO2004072084 (US20050256152, EP 1480985 B1) and WO2004072085. Subsequently, Helm disclosed non-solvated forms in their application no. US20050203122.
We have disclosed new polymorphic forms of Clopidogrel mesylate, Clopidogrel besylate and Clopidogrel tosylate in our published Application No. WO 2004106344, which are stable, free flowing, scalable, useful industrially and have important pharmacological properties. We herein disclose improved processes for preparing different forms of (S)-(+) Clopidogrel besylate.